The Genomics/Genetics Core will be responsible for providing high-throughput gene expression data, including validation of expression of select candidate genes, as well as genotyping and sequencing services, to include DMA and RNA isolation, quantification, plating and tracking, in order to achieve the overall aims of the Hopkins Rheumatic Disease Research Core Center (RDRCC). This Core will support the procurement and analysis of tissue samples from a variety of complex rheumatic disorders, including scleroderma, lupus, arthritis, and vasculitis. In genomics studies, patterns of gene expression will be analyzed within each clinical and experimental condition. This approach will allow us to determine both concordantly and discordantly regulated gene clusters, link these gene clusters with physiological measurements of traits, and determine the gene profiles responsible for the development and maintenance of well-defined phenotypes. The genetics component will facilitate the validation of the physiological importance of genes and "high risk" alleles in well-characterized cohorts, providing services that will enable Investigators to detect novel variants and to test for association of variants in candidate genes for a variety of rheumatic diseases. Through microarray analysis, we will be able to explore novel sentinel genes and regulatory pathways involved in rheumatic diseases and facilitate the selection of candidate genes for high-throughput genotyping. The Core will interact directly with Core A, which will assist the Core with financial management, integrate information technology solutions with the Core's database system, and coordinate the development of new research endeavors by individual investigators. These data will be linked through Core B for downstream functional studies of genes identified in Core C. These comprehensive human genomic studies will complement the rigorous phenotypic characterization provided by Investigators in the Research Base. Specific Aims of the Core are: 1) to provide an integrated laboratory needed to support gene expression profiling and genotyping on samples from well-characterized patients with rheumatic disorders, experiment and project management, primer and assay design, and computational/analytical activities associated with genomic and genetic data; 2) provide an efficient, cost-effective high-throughput expression profiling and genotyping service to meet the demands of diverse individual projects, including a pilot project as part of the RDRCC which aims to test for association of genetic variants in a priority candidate gene for scleroderma, granzyme B (GZMB).